1. Field of the Invention
The present invention relates to a chemical sensor element and a method for fabricating the same.
2. Description of the Related Art
Heretofore, methods for measuring a change between before and after the antigen-antibody reaction of an antibody or an antigen adsorbed on fine metal particles with the antigen or the antibody by utilizing localized surface Plasmon resonance have been known. For example, U.S. Pat. No. 5,607,643 discloses a method for detecting localized surface Plasmon resonance by a Raman spectrum and Raman scattering intensity. By this method, an antigen of a substance to be measured is added to the surfaces of fine metal particles on which an antibody has been previously adsorbed to cause an antigen-antibody reaction and form an immune complex. The formed immune complex can be identified from the Raman spectrum in this state. Further, it is disclosed that the added objective substance can be quantitatively determined from Raman scattering intensity on the surface of fine metal particles adsorbing the immune complex.
A biosensor that can be applied to the present invention is a measuring device utilizing an excellent biological molecular recognizing ability of living organisms or biological molecules. It has wide applications not only in the medical fields, but is also expected to be applicable in the environmental or food areas.
In general, a biosensor includes a capturing substance to recognize and capture a substance to be measured (hereafter referred to as “target substance”), and a detecting element to detect physical and chemical change that occurred at the time and convert the change to a signal that can be detected, such as an electrical signal and an optical signal. In living organisms, there are combinations of substances with affinity for each other, such as enzyme-substrate, antigen-antibody and DNA-DNA. The biosensor utilizes the principle wherein a component of these combinations can be selectively measured by disposing the other component on or in a base material to use as a capturing substance component. As the detecting element, various systems, such as an oxygen electrode, a hydrogen peroxide electrode, an ion electrode, ISFET and a thermistor are proposed. Recently, a quartz oscillator, an SAW element or the like that can detect a change in mass on a nanogram scale, may be used.
The measuring method utilizing localized surface Plasmon resonance employs a simple configuration of the assay because labeling molecules, for example with a fluorescent colorant, is not required; and the process of an adsorbing reaction onto the surfaces of fine metal particles can be directly monitored in real time. Therefore, the application of the measuring method utilizing localized surface Plasmon resonance to various assays is expected. An example of such an application is an affinity assay, such as an immunoassay utilizing the specificity of the antigen-antibody reaction.
Japanese Patent No. 3,452,837 (Japanese Patent Application Laid-Open No. 2000-356587) discloses, as a sensor element that can be effectively used in affinity assay, a localized surface Plasmon resonance sensor wherein a plurality of fine metal particles are fixed on a substrate, and the refractive index of the medium using the Plasmon resonance of the fine metal particles is determined.
However, in a sensor element of the configuration wherein fine metal particles are fixed on a substrate utilizing localized surface Plasmon resonance, fine metal-containing particles may be aggregated, or may be disposed on the substrate at an extremely uneven density, during cleaning or drying in the process of fabricating the sensor element. In addition, fine metal-containing particles may also aggregate during cleaning or drying in an assay detection using the above-described sensor element. As a result, the detection sensitivity of the sensor may be extremely reduced. Specifically, aggregation of metal-containing particles is a big problem in the face of expanding the application of the measuring method utilizing localized surface Plasmon resonance.
Furthermore, there is a tendency for the metal-containing particles to become aggregated easier if their concentration is elevated. Consequently, the disposition of metal-containing particles on the substrate at a high density may become difficult.